Pandemic outbreaks of highly virulent avian influenza present a serious risk to human and animal health worldwide. Genetic reassortment between human and avian influenza viruses can result in a virus with a novel hemagglutinin (HA) of avian origin, against which humans lack immunity. In the 20th century, the pandemics of 1918, 1957 and 1968 were the result of such antigenic shifts. The recent outbreaks of avian influenza caused by H5N1, H7N7 and H9N2 subtype influenza viruses, and their infection of humans have created a new awareness of the pandemic potential of influenza viruses that circulate in domestic poultry. The estimated economic impact of a pandemic would be up to $165 billion in the United States alone, with as many as 200,000 deaths, 730,000 hospitalizations, 42 outpatient visits, and 50 million additional illnesses.
In the context of prevailing threats of global bioterrorism, individuals deliberately infected with a highly virulent influenza strain could act as difficult-to-detect biological weapons of mass destruction.
To date, three major approaches to developing a safe and effective vaccine against potentially pandemic avian influenza strains have been attempted, none of which is entirely successful (Wood et al., Vaccine 20:S84-S87, 2002; Stephenson et al., The Lancet 4:499-509, 2004, and references cited therein).
Due to the lethality of these influenza strains in poultry, current vaccine production strategies involving growth of virus in hen's eggs are not feasible. Some approaches have focused on isolating non-pathogenic or attenuated strains of influenza that express the relevant immunogenic antigens of the potentially pandemic influenza strains. For example, naturally occurring, apathogenic strains of influenza with the H5 subtype antigen virus have been evaluated as vaccine candidates. In general, these viruses have proved difficult to grow using conventional technology, and protection is dependent on the ability of antibodies raised against the apathogenic vaccine strain to cross-react with the virulent strain of virus (Takada et al., J. Virol. 73:8303-8307, 1999; Wood et al., Vaccine 18:579-80, 2000). A reverse genetics approach has been employed to delete a stretch of basic amino acids at the cleavage site of the HA antigen of a pathogenic H5N1 virus (A/HK/97) to develop a candidate vaccine (Li et al., J. Infect. Dis. 179:1132-1138, 1999).
Another approach has been to utilize recombinant HA (“H5”) produced in a baculovirus expression system. However, high doses of purified protein and the use of adjuvants are required to achieve a satisfactory immune response. (Treanor et al. Vaccine 19:1732-1737, 2001).
There remains a need to develop vaccines that are protective against infection by avian influenza strains in both human and non-human populations, and which can be efficiently produced and administered without reliance on viral growth in hen's eggs. The present disclosure addresses this need, and provides novel compositions and methods useful for preventing infection by avian and pandemic influenza strains.